Desensitizing Effect of Cancer Cachexia on Immune Checkpoint Inhibitors in Patients With Advanced NSCLC

Miyawaki, Taichi; Naito, Tateaki; Kodama, Akihro; Nishioka, Naoya; Miyawaki, Eriko; Mamesaya, Nobuaki; Kawamura, Takahisa; Kobayashi, Hiroyoshi; Omori, Shota; Wakuda, Kazushige; Ono, Akira; Kenmotsu, Hirotsugu; Murakami, Haruyasu; Notsu, Akifumi; Mori, Keita; Harada, Hideyuki; Endo, Masahiro; Takahashi, Kazuhisa; Takahashi, Toshiaki

doi:10.1016/j.jtocrr.2020.100020

Cited by 34 publications

(44 citation statements)

References 33 publications

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“…There are no data on clinically useful predictors for host antitumor immunity 6,7 . Recently, we proposed a hypothesis regarding the suppressive effects of cancer cachexia on PD‐1/PD‐L1 inhibitors in patients with metastatic non‐small cell lung cancer (NSCLC) 8 . Patients with cachexia exhibited worse overall response rate (ORR) and progression free survival (PFS) values than those without it, even if they were potentially sensitive to anti‐programed cell death 1/programed cell death ligand 1 (PD‐1/PD‐L1) inhibitor and have high PD‐L1 expression in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

“…6,7 Recently, we proposed a hypothesis regarding the suppressive effects of cancer cachexia on PD-1/PD-L1 inhibitors in patients with metastatic non-small cell lung cancer (NSCLC). 8 Patients with cachexia exhibited worse overall response rate (ORR) and progression free survival (PFS) values than those without it, even if they were potentially sensitive to anti-programed cell death 1/programed cell death ligand 1 (PD-1/PD-L1) inhibitor and have high PD-L1 expression in cancer cells. Impaired nutritional status 9 potentially attenuated the host antitumor immunity in a preclinical study, and several other studies that measured the bodyweight of patients with NSCLC supported our findings.…”

Section: Introductionmentioning

confidence: 99%

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Unfavorable impact of decreased muscle quality on the efficacy of immunotherapy for advanced non‐small cell lung cancer

et al. 2020

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Unfavorable impact of decreased muscle quality on the efficacy of immunotherapy for advanced non‐small cell lung cancer

et al. 2020

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“…Several previous studies have demonstrated that cancer cachexia or sarcopenia adversely affects the clinical outcome of PD-1 or PD-L1 inhibitor monotherapy. [11,12] Meanwhile, no previous studies have evaluated the e cacy of PD-1/PD-L1 inhibitor plus chemotherapy, the current standard primary treatment for advanced NSCLC, separately in the existence of cancer cachexia, as shown in this study. Although cancer cachexia has an adverse impact on clinical outcomes among patients with advanced NSCLC, it has not been incorporated as a stratifying factor in most clinical trials.…”

Section: Discussionmentioning

confidence: 92%

“…Furthermore, cancer cachexia potentially has a desensitizing effect in patients with high PD-L1 expression who potentially have an increased sensitivity to PD-1 or PD-L1 inhibitors. [12] PD-1/PD-L1 inhibitor plus chemotherapy might not be effective for all patients with advanced NSCLC. [5][6][7] Thus, it is essential to identify populations that do not respond to PD-1/PD-L1 plus chemotherapy to achieve further survival bene ts.…”

Section: Introductionmentioning

confidence: 98%

Impact of Cancer Cachexia on Treatment With PD-1/PD-L1 Inhibitors Plus Chemotherapy in Advanced Non-small-Cell Lung Cancer

Miyawaki

Naito

Yabe

et al. 2021

Preprint

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PurposeProgrammed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors plus chemotherapy has become the standard first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC). However, few studies have explicitly focused on the impact of cancer cachexia on the efficacy of PD-1/PD-L1 inhibitors plus chemotherapy. Thus, we evaluated the clinical implications of cancer cachexia on the survival outcomes in patients who received this treatment.MethodsWe conducted a retrospective review of medical records of patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors plus chemotherapy from December 2018 to December 2020. Cancer cachexia was diagnosed as an unintentional weight loss of 5% or more over six months. We evaluated the progression-free survival (PFS) and overall survival (OS) for patients with or without cancer cachexia who received PD-1/PD-L1 inhibitors plus chemotherapy.ResultsAmong the 80 included patients, 37 (46%) had cancer cachexia. Cachectic patients had a lower objective response rate (30 vs 51%, P <0.05), poorer PFS (2.3 vs 12.0 months, P <0.05), and poorer OS (10.8 vs 23.9 months, P <0.05) than non-cachectic patients. The Cox proportional-hazard ratios (95% confidence interval) of cancer cachexia were 1.77 (1.01–3.10) for PFS and 2.90 (1.40–6.00) for OS, with adjustments for Eastern Cooperative Oncology Group performance status, PD-L1 tumour proportion score, histology, and central nervous system metastases. ConclusionPre-treatment cancer cachexia may reduce treatment efficacy and shorten survival time in patients receiving PD-1/PD-L1 inhibitors plus chemotherapy. Early evaluation and intervention for cancer cachexia might improve oncological outcomes in patients with advanced NSCLC.

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“…It has been reported that cancer cachexia may be a poor prognostic factor for disease control and survival after ICI monotherapy. [16][17][18] However, there are few reports investigating whether cancer cachexia is a prognostic factor for chemoimmunotherapy in patients with NSCLC. This study investigated the impact of cancer cachexia on the therapeutic outcome of combined chemoimmunotherapy in patients with NSCLC.…”

Section: Introductionmentioning

confidence: 99%

Impact of cancer cachexia on the therapeutic outcome of combined chemoimmunotherapy in patients with non-small cell lung cancer: a retrospective study

et al. 2021

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Although previous studies suggest that cancer cachexia is a poor prognostic factor for immune checkpoint inhibitor monotherapy, the impact of cancer cachexia on chemoimmunotherapy is unclear. We investigated the impact of cancer cachexia on the therapeutic outcomes of chemoimmunotherapy for non-small cell lung cancer (NSCLC). We retrospectively analyzed patients' medical records with NSCLC who received chemoimmunotherapy in 12 institutions in Japan between January and November 2019. We defined cancer cachexia as weight loss exceeding 5% of the total body weight or a body mass index of < 20 kg/m 2 and weight loss of more than 2% of the total body weight within 6 months before chemoimmunotherapy initiation, with laboratory results exceeding reference values. This study enrolled 235 patients with NSCLC, among whom 196 were eligible for analysis, and 50 (25.5%) met the criteria for cachexia diagnosis. Patients with cancer cachexia had a significantly higher frequency of a programmed death-ligand 1 (PD-L1) expression of ≥ 50% (48%, p = .01) and shorter progression-free survival (PFS; logrank test: p = .04) than patients without cachexia. There was no significant difference in overall survival (OS) between the cachexia and no-cachexia groups (log-rank test: p = .14). In the PD-L1 ≥ 50% population, there was no significant difference in PFS and OS (log-rank test: p = .19 and p = .79, respectively) between patients with NSCLC in the cachexia or no-cachexia groups. Cancer cachexia might be a poor prognostic factor in patients with NSCLC receiving chemoimmunotherapy.

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Desensitizing Effect of Cancer Cachexia on Immune Checkpoint Inhibitors in Patients With Advanced NSCLC

Abstract: Introduction: Programmed cell death 1 (PD-1) inhibitors have become standard treatment for patients with advanced NSCLC. However, few studies have focused on the impact of cancer cachexia on the efficacy of PD-1 or programmed death-ligand 1 (PD-L1) inhibitors among patients with NSCLC.

Cited by 34 publications

References 33 publications

Unfavorable impact of decreased muscle quality on the efficacy of immunotherapy for advanced non‐small cell lung cancer

Unfavorable impact of decreased muscle quality on the efficacy of immunotherapy for advanced non‐small cell lung cancer

Impact of Cancer Cachexia on Treatment With PD-1/PD-L1 Inhibitors Plus Chemotherapy in Advanced Non-small-Cell Lung Cancer

Impact of cancer cachexia on the therapeutic outcome of combined chemoimmunotherapy in patients with non-small cell lung cancer: a retrospective study

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